The mammalian eye serves both visual and non-image-forming functions. Until recently, clinical and research attention has focused on visual function. However, new work has begun to characterize the anatomy and physiology of the non-image-forming responses. Some of these responses are due to the effect of light on circadian rhythms, the endogenous ~24-hour rhythms generated by a pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. This pacemaker is entrained to environmental time using ocular light stimuli primarily mediated by intrinsically photosensitive retinal ganglion cells, rather than rod and cone photoreceptors. The outputs of the SCN influence almost every physiologic function, including the timing and content of sleep, hormone release, cardiovascular and gastrointestinal function, neurocognitive objective performance, subjective alertness, and mood. Disruption of the circadian pacemaker or of its normal phase relationship with local time, such as with night or rotating work shifts or jet lag, is associated with illness, errors and accidents. Other non-visual effects of ocular light exposure include melatonin suppression (signal for seasonal reproductive changes), pupillary reflexes, and changes in heart rate, performance, and alertness. Because light is the most potent stimulus for these functions, it is important to understand what characteristics of light are most effective. We will complete a dose response curve for light duration using experimental, modeling, and database approaches. Experimentally, we will quantify the effects of ocular light stimuli of 2 and 12 minute durations - stimuli that were previously considered too short to have an effect, but may induce significant physiologic changes. We also will investigate the duration of darkness exposure required to reset circadian sensitivity. The effects of light on other functions, including melatonin suppression, heart rate, and alertness will also be studied. The data from these experiments will be combined into a database with data from over 2000 subjects already studied in similar protocols on the effects of light duration, intensity, timing and wavelength on the human circadian pacemaker, melatonin suppression, heart rate, cognitive responses and sleep. All these data then will be used to refine our validated mathematical model of the effects of light on the human circadian pacemaker, which, with countermeasure applications, will be made available on the internet. This work is relevant for understanding the basic physiology of human circadian, hormone, heart rate, performance and alertness functions in response to ocular light stimuli, with implications for retinal/eye care;sleep of older persons;and altered performance/ alertness. If very short light stimuli are effective, then ocular light stimuli as countermeasures for poor performance and alertness would be applicable in more situations than currently believed. The results can be used to make predictions about the effects of light, to make recommendations involving exposure to or avoidance of light, and to design environmental lighting (e.g., room or desk lights), resulting in improved health and alertness and decreased errors and accidents. PUBLIC HEALTH RELEVANCE: The mammalian eye serves both visual and non-image-forming functions. New information about the non- image-forming anatomy and physiology of the eye has revealed effects of ocular light stimuli on human circadian rhythms, melatonin suppression, heart rate, pupillary reflexes, cognitive performance, alertness and sleep. The results of the proposed work can be used to make predictions about the effects of light, to make recommendations involving exposure to or avoidance of light, and to design environmental lighting, resulting in improved health and alertness and decreased errors and accidents.